• Adolescence;
  • cannabis use;
  • cortisol;
  • HPA axis;
  • stress-reactivity;
  • tobacco use


Aims  To investigate the relationship of life-time and repeated cannabis use with hypothalamic–pituitary–adrenal (HPA) axis reactivity to social stress in a general population sample of adolescents.

Design  Adolescents who reported life-time or repeated cannabis use, life-time or repeated tobacco use and never use of either cannabis or tobacco were compared with respect to their HPA axis reactivity during the Groningen Social Stress Task (GSST), which was based on the Trier Social Stress Task.

Setting  A large prospective population study of Dutch adolescents [the TRacking Adolescents' Individual Lives Survey (TRAILS) study].

Participants  A total of 591 adolescents (51% male) who participated in the GSST, which was an additional measurement during the third assessment wave.

Measurements  HPA axis stress-reactivity was indexed by four cortisol samples collected before, during and after the GSST. Furthermore, all adolescents in our study completed self-reported questionnaires on life-time and repeated cannabis and tobacco use. Models were adjusted for sex, recent alcohol use, experimental session risk status, socio-economic status, mood and time of the experimental session.

Findings  Life-time cannabis users had significantly lower stress-reactivity levels when compared to abstainers [odds ratio (OR) = 0.68, confidence interval (CI) = 0.55–0.85, P < 0.01] and life-time tobacco users (OR = 0.79, CI = 0.64–0.98, P < 0.05). In addition, repeated cannabis users also exhibited lower stress-reactivity levels when compared to life-time ever users of either tobacco or cannabis (OR = 0.74, CI = 0.53–0.98, P < 0.05).

Conclusions  Lower hypothalamic–pituitary–adrenal-axis stress-reactivity in adolescents is related specifically to life-time and repeated cannabis use.